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Benefit Ledger · verified · Biology

ESM3 generates esmGFP, a distant functional fluorescent protein

EvolutionaryScale’s ESM3 language model produced esmGFP, a fluorescent protein about 58 percent identical to known GFPs, described in a 2024 preprint and a 2025 Science paper.

16 Jan 2025Tier 3 MajorMethodology 0.1

Current score

+2.06

10 base · Major (tier 3 of 5, 10 pts)
× 0.8500 attribution · Primary causal contribution
× 0.7000 evidence · Peer review or independent validation
× 0.5500 realization · Experimentally validated
× 0.7000 durability
Event-level product before credit split: 2.29

Experimentally functional de novo-distant GFP is a major protein-design result (tier 3). High attribution. Science peer review. Realization is a characterized protein, not a therapeutic. Sequence and method are durable knowledge.

What happened

ESM3 is a multimodal generative model over protein sequence, structure, and function. Iterative prompting and wet-lab screening yielded esmGFP, which the authors compared to hundreds of millions of years of natural GFP divergence. Experimental fluorescence was confirmed; maturation was slower than many natural GFPs. The “500 million years” phrasing is an interpretive evolutionary-distance analogy, not a literal simulation of history.

Model attribution

+2.06

ESM

Generated candidate fluorescent-protein sequences that were expressed and assayed.

Model proposed sequences; humans selected, synthesized, and assayed.

Attribution 0.8500 · Credit share 90% · EvolutionaryScale

Claims

  • ESM3-designed esmGFP fluoresced and is about 58 percent identical to the nearest known fluorescent protein.

    outcome · supported

  • ESM3 literally simulated 500 million years of natural evolution.

    significance · disputed

Sources

primary sources

Secondary domains: Chemistry

Revision history

  • 13 Sep 2026 · 0.00 → 2.06

    Initial adjudicated seed score under methodology 0.1.